Repellent substances generally cause insects to be driven away from, or to reject, otherwise insect-acceptable food sources or habitats. At least 85% of insect repellent sales in the United States are for insect repellents containing N,N-diethyl-m-toluamide (DEET) as their primary active ingredient. Further, Consumer Reports tests indicated that products with the highest concentration of DEET lasted the longest against mosquitoes. Although an effective repellent, DEET possesses an unpleasant odor and imparts a greasy feeling to the skin. Other disadvantages associated with DEET include: 1) it is a synthetic chemical, that is, it is not derived from natural sources; 2) it exhibits a somewhat limited spectrum of activity—it is not, for example, as effective as might be desired against black-legged or deer ticks (Schreck, C. E., Fish, D. & McGovern, T. P. (1995) Journal of the American Mosquito Control Association 11(1), 136-140); 3) DEET dissolves or mars many plastics and painted surfaces; and 4) DEET may plasticize some inert ingredients typically used in topical formulations which leads to lower user acceptability.
As a result of the above limitations, DEET-free products with repellent activity are finding favor with consumers. In particular, demand for compositions containing natural products is increasing. New candidate repellents should possess a desirable balance of properties, and will preferably reach or exceed the positive properties of DEET, and/or not suffer from its negative properties (Holton, T. (2003) The Scientist Jun. 16, 2003, 25-26).
Many plant species produce essential oils (aromatic oils) which are used as natural sources of insect repellent and fragrant chemicals [Hay, R. K. M., Svoboda, K. P., Botany, in ‘Volatile Oil Crops: their biology, chemistry and production’. Hay, R. K. M., Waterman, P. G. (eds.). Longman Group UK Limited (1993)]. Citronella oil, known for its general repellence towards insects, is obtained from the graminaceous plants Cymbopogon winterianus and C. nardus. Examples of plants used as sources of fragrant chemicals include Melissa officinalis (Melissa), Perilla frutescens (Perilla), Posostemon cablin (Patchouli) and various Lavandula spp. (Lavender). All of these examples of plants yielding oils of value are members of the Labiatae (Lamiaceae) family. Plants of the genus Nepeta (catmints) are also members of this family, and produce an essential oil that is a minor item of commerce. This oil is very rich in a class of monoterpenoid compounds known as iridoids [Inouye, H. Iridoids. Methods in Plant Biochemistry 7:99-143 (1991)], more specifically the methylcyclopentanoid nepetalactones [Clark, L. J. et al. The Plant Journal, 11:1387-1393 (1997)] and derivatives.
Iridoid monoterpenoids have long been known to be effective repellents to a variety of insect species (Eisner, T. (1964) Science 146:1318-1320; Eisner, T. (1965) Science 148:966-968; Peterson, C. and Coats, J. (2001) Pesticide Outlook 12:154-158; Peterson, C. et al. (2001) Abstracts of Papers American Chemical Society 222 (1-2): AGRO73). Studies of the repellency of catnip oil (predominantly nepetalactone) showed that it was repellent towards a number of insect species on short-term exposure, but not to a number of other species (Eisner, T. (1964) Science 146:1318-1320).
U.S. Pat. No. 4,663,346 discloses insect repellants with compositions containing bicyclic iridoid lactones (e.g., iridomyrmecin). Further, U.S. Pat. No. 4,869,896 discloses use of these bicyclic iridoid lactone compositions in potentiated insect repellent mixtures with DEET. U.S. Pat. No. 6,524,605 discloses insect repellents comprising nepetalactones derived from the catmint plant N. cataria, and the differential efficacy of nepetalactone stereoisomers as insect repellents.
Compositions containing dihydronepetalactones (DHN), a class of iridoid monoterpenoids derived from nepetalactones (shown in FIG. 1), are known to provide insecticidal effects. For example, a study of the composition of the secretion from anal glands of the ant Iridomyrmex nitidus showed that isodihydronepetalactone was present in appreciable amounts, together with isoiridomyrmecin (Cavill, G. W. K., and D. V. Clark. (1967) J. Insect Physiol. 13:131-135). Isoiridomyrmecin was known at the time to possess good ‘knockdown’ insecticidal activity.
Cavill et al. (1982) (Tetrahedron 38:1931-1938), discloses the presence of dihydronepetalactones in the insect repellent secretion of an ant but the compound iridodial is said to be the principal repellent constituent.
Jefson, M., et al. (1983) (J. Chemical Ecology 9:159-180) disclose dihydronepetalactone to exhibit effective repellency in the vapor phase to ants over a period of 25 seconds. Longer times were not investigated. After 25 seconds of exposure to vapors from the pure dihydronepetalactone, approximately 50-60% of Monomorium destructor ants ceased to feed. No indication was given in regard to the duration of the repellent effect.